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Publication : p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia.

First Author  Pignon JC Year  2013
Journal  Proc Natl Acad Sci U S A Volume  110
Issue  20 Pages  8105-10
PubMed ID  23620512 Mgi Jnum  J:197339
Mgi Id  MGI:5492195 Doi  10.1073/pnas.1221216110
Citation  Pignon JC, et al. (2013) p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia. Proc Natl Acad Sci U S A 110(20):8105-10
abstractText  The tumor protein p63 (p63), and more specifically the NH2-terminal truncated (DeltaN) p63 isoform, is a marker of basal epithelial cells and is required for normal development of several epithelial tissues, including the bladder and prostate glands. Although p63-expressing cells are proposed to be the stem cells of the developing prostate epithelium and bladder urothelium, cell lineages in these endoderm-derived epithelia remain highly controversial, and rigorous lineage tracing studies are warranted. Here, we generated knock-in mice expressing Cre recombinase (Cre) under the control of the endogenous DeltaNp63 promoter. Heterozygote DeltaNp63(+/Cre) mice were phenotypically normal and fertile. Cre-mediated recombination in DeltaNp63(+/Cre);ROSA26(EYFP) reporter mice faithfully recapitulated the pattern of DeltaNp63 expression and were useful for genetic lineage tracing of DeltaNp63-expressing cells of the caudal endoderm in vivo. We found that DeltaNp63-positive cells of the urogenital sinus generated all epithelial lineages of the prostate and bladder, indicating that these cells represent the stem/progenitor cells of those epithelia during development. We also observed DeltaNp63 expression in caudal gut endoderm and the contribution of DeltaNp63-positive cells to the stem/progenitor compartment of adult colorectal epithelium. Because p63 is a master regulator of stratified epithelial development, this finding provides a unique developmental insight into the cell of origin of squamous cell metaplasia and squamous cell carcinoma of the colon.
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